Cardiovascular disease (CVD) is the leading cause of death, major disease and disability among U.S. men and women, according to background information in the article. Major depression was found in approximately 20 percent of patients with a recent myocardial infarction (MI; heart attack); a similar prevalence was found for minor depression. Depression is a risk factor for recurrent non-fatal heart attack and cardiac death in patients who experience an acute MI (AMI), independent of cardiac disease severity. Despite their effectiveness in treating depression, the use of antidepressants in patients with CVD remains controversial.
C. Barr Taylor, M.D., from Stanford Medical Center, Stanford, Calif., and colleagues conducted a secondary analysis of data from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial to determine the effects of antidepressants on post-MI patients. The ENRICHD trial randomized 2,481 depressed and/or socially isolated patients from October 1, 1996 to October 31, 1999. The analysis in this report is based on 1834 patients (985 men and 849 women) who had depression, with or without low social support. Of these, 446 patients took antidepressants during the study, including 301 who were prescribed SSRIs (a class of drugs that increases the levels of serotonin in the body); and 145 patients who were prescribed other types of antidepressants.
During an average follow-up of 29 months, 457 fatal and non-fatal cardiovascular events occurred. Twenty-six percent (361 of 1,388) of the patients who did not receive antidepressants died or had a recurrent MI, compared to 21.5 percent (96 of 446) of the patients who did take antidepressants. After adjusting for baseline depression and cardiac risk, SSRI use was associated with 43 percent lower risk of death or recurrent non-fatal MI, and 43 percent lower risk of death from all causes, compared with patients not receiving SSRIs. Risk of death or recurrent MI, all-cause death, or recurrent MI was 28 percent, 36 percent, and 27 percent lower, respectively, in patients taking non-SSRI antidepressants, compared with nonusers.
"The main finding of this study is that antidepressant use post-AMI by depressed patients in the ENRICHD clinical trial was associated with significantly lower rates of the study primary end points, death and reinfarction [recurrent heart attack]," the authors write.
(Arch Gen Psychiatry. 2005; 62: 792-798. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: This study was supported by contracts from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Editorial: Does Treating Post-Myocardial Infarction Depression Reduce Medical Mortality?
In an editorial accompanying this study, Alexander H. Glassman, M.D., of the New York State Psychiatric Institute, writes that in the ENRICHD trial "only the most depressed patients, those known to be at higher risk for cardiac events, were offered antidepressants. In addition, there was no control over when the drug was started or stopped, and even the reported start and stop times were only estimates. However, the sample was large, the number of events reasonable, and the magnitude of the effect is hard to ignore. Had the ENRICHD study observed an uncontrolled 40 percent increase in mortality with antidepressant drug treatment, public advocates would be clamoring for review by the Food and Drug Administration, label changes, or even 'black box' warnings. Yet this observation of a 40 percent decrease in life-threatening outcomes has been in the literature for almost three years with no systematic follow-up and minimal medical or psychiatric awareness."
"There are multiple mechanisms by which depression could increase vascular disease," Dr. Glassman writes. "It increases platelet activation and inflammatory markers, reduces heart variability, and leads to multiple adverse health behaviors; all are associated with increased cardiovascular risk and death. Whatever links depression and heart disease, it is more likely to involve all of the above rather than any single pathway."
"Acknowledging the implications of MDD [major depressive disorder] for cardiac morbidity and mortality would validate depression as a systemic disease with implications for the entire body, and reduce the stigma of this diagnosis for medical professionals, the public, and the patients themselves," Dr. Glassman concludes. "The ENRICHD investigators have made a significant step in that direction."
(Arch Gen Psychiatry. 2005; 62: 711-712. Available pre-embargo to the media at www.jamamedia.org.)
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Journal
Archives of General Psychiatry